Early genetic restoration of lubricin expression in transgenic mice mitigates chondrocyte peroxynitrite release and caspase-3 activation
OSTEOARTHRITIS AND CARTILAGE
Authors: Larson, K. M.; Zhang, L.; Badger, G. J.; Jay, G. D.
Abstract
Objective: This study investigated the ability of endogenous lubricin secretion to restore joint health following a brief <21 day, postnatal lubricin-null state, in a C57BL/6J Prg4 gene trap (GT) mouse under the control of cre-recombinase. Previously we showed that re-expression of lubricin at 21 days was partly restorative of joint lubrication. Design: The tibio-femoral joints of adult C57BL/6J mice containing lubricin, lacking lubricin, and postnatally lacking lubricin until restoration of lubricin expression at 7 days or 14 days of age were evaluated ex vivo. At 8-weeks of age, whole joint coefficient of friction (COF), and caspase-3 activation were measured and the tibial-femoral joints histologically analyzed for degenerative changes, following progressive cyclic loading. The peroxynitrite content of femoral head cartilage from these mice prior to cyclic loading was measured. Results: Mice that underwent gene recombination at 7 and 14 days of age did not reestablish low COF as joint cycling time increased and were histopathologically indistinguishable from the joints of lubricin-null littermates. However, cartilage from tibio-femoral joints that underwent recombination at 7 and 14 days of age had significantly fewer caspase-3 positive cells and significantly reduced peroxynitrite content compared to lubricin-null littermates. Conclusions: The biological effects of lubricin, which include limiting inflammation via peroxynitrite production and caspase-3 activation, may be achieved without completely restituting low COF. However, fully recapitulating low COF may require undamaged cartilage surfaces or absence of biofouling, which may interfere with the activity of lubricin. (C) 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Association of lubricin concentration in synovial fluid and clinical status of osteoarthritic knee
MODERN RHEUMATOLOGY
Authors: Ogawa, Hiroyasu; Matsumoto, Kazu; Terabayashi, Nobuo; Kawashima, Kenji; Takeuchi, Kentaro; Akiyama, Haruhiko
Abstract
Objectives: Although lubricin plays a role in controlling inflammation and pain as well as being a mechanical lubricant, clinical relevance of lubricin concentration in synovial fluid (SF) is unknown. The purpose was to determine whether lubricin concentration in SF is associated with the clinical status of the knee.Methods: SF was obtained from 61 knee joints from patients who underwent any knee surgery with several stages of knee osteoarthritis. Lubricin/PRG4 concentration in SF was measured by enzyme-linked immunosorbent assay (ELISA). Clinical evaluations of the knee by the Kellgren and Lawrence (K-L) system, Knee Society Score (KSS), and the range of knee motion, and assessment of joint laxity were performed. Association of lubricin concentration in SF and these clinical factors was statistically analyzed.Results: There was no significant correlation between lubricin concentration in SF and age, sex, K-L grade, or KSS. However, lubricin concentration was significantly correlated with anteroposterior laxity (R=0.50, p<0.001), full flexion angle (R=0.39, p<0.01), and range of knee motion (R=0.38, p<0.01), but not full extension angle, varus laxity, or valgus laxity.Conclusions: Lubricin concentration was correlated with joint flexibility, but not with clinical symptoms, including pain at that time.